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泛素化在核苷酸切除修复调控中的多重作用。

Multiple roles of ubiquitination in the control of nucleotide excision repair.

机构信息

Institute for Cancer Studies, University of Sheffield, Sheffield S10 2RX, UK.

出版信息

Mech Ageing Dev. 2011 Aug;132(8-9):355-65. doi: 10.1016/j.mad.2011.03.003. Epub 2011 Apr 2.

Abstract

Nucleotide excision repair (NER) is a remarkably versatile DNA repair system, essential for maintenance of genomic stability. Hereditary alterations in NER enzymes can result in increased cancer propensity, but also in developmental, neurodegenerative, and progeroid syndromes. NER can be operationally divided in three subtypes, which share many common steps: global genomic repair (GGR) operates on the whole genome level, transcription domain-associated repair (DAR) is a concentration of NER activity within transcription factories, and transcription-coupled repair (TCR) provides faster repair of the transcribed strand of active genes. Interestingly, ubiquitination plays an important role in all three classes of NER, as well as in associated phenomena, such as damage signalling by histone ubiquitination, and degradation of stalled RNA polymerase II when repair does not occur in a timely manner.

摘要

核苷酸切除修复(NER)是一种非常灵活的 DNA 修复系统,对于维持基因组稳定性至关重要。NER 酶的遗传改变可导致癌症易感性增加,但也可导致发育、神经退行性和早衰综合征。NER 可以在操作上分为三个亚型,它们有许多共同的步骤:全基因组修复(GGR)在整个基因组水平上运作,转录域相关修复(DAR)是转录工厂内 NER 活性的集中,转录偶联修复(TCR)为活跃基因的转录链提供更快的修复。有趣的是,泛素化在所有三种 NER 类型以及相关现象中都起着重要作用,例如组蛋白泛素化的损伤信号,以及当修复不能及时发生时 RNA 聚合酶 II 的失活。

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